Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP)
- 29 January 2009
- journal article
- research article
- Published by Wiley in Acta Paediatrica
- Vol. 98 (3), 482-489
- https://doi.org/10.1111/j.1651-2227.2008.01131.x
Abstract
Aims: Mice lacking pituitary adenylate cyclase‐activating polypeptide (PACAP) are prone to sudden death in the second post‐natal week, having respiratory and metabolic disturbances reminiscent of the human Sudden Infant Death Syndrome (SIDS). Here we test the hypothesis that the human PACAP gene is a site of genetic variance associated with SIDS in a cohort of 92 victims and 92 matched controls. Methods: Using polymerase chain reaction and sequencing, we examined the PACAP gene in 92 SIDS cases (46 Caucasians and 46 African Americans) and 92 race‐ and gender‐matched controls. Results: We found no significant associations between PACAP and SIDS in Caucasians. However, in the African Americans, a non‐synonymous single nucleotide polymorphism (i.e. an aspartic acid/glycine coding variant, rs2856966) within exon 2 of PACAP was significantly associated with SIDS (p = 0.004), as were haplotypes containing this polymorphism (p < 0.0001). Glycine was three times more likely at this location in the African‐American SIDS victims (17 cases) than African‐American controls (5 cases). Conclusion: These data are the first to suggest an association between a variant within the coding region of the PACAP gene and SIDS. Based on these findings, further investigations are warranted into the functional importance of PACAP signaling in neonatal survival and the role of PACAP‐signaling abnormalities in SIDS.Keywords
This publication has 53 references indexed in Scilit:
- A Functional Polymorphism in the Tyrosine Hydroxylase Gene Indicates a Role of Noradrenalinergic Signaling in Sudden Infant Death SyndromeThe Journal of Pediatrics, 2008
- Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndromeHeart Rhythm, 2008
- Tragic and sudden deathEMBO Reports, 2008
- A mechanism for sudden infant death syndrome (SIDS): Stress-induced leak via ryanodine receptorsHeart Rhythm, 2007
- Novel mechanism for sudden infant death syndrome: Persistent late sodium current secondary to mutations in caveolin-3Heart Rhythm, 2006
- Sudden infant death syndrome: Case‐control frequency differences in paired like homeobox (PHOX) 2B geneAmerican Journal of Medical Genetics Part A, 2006
- Nicotine metabolizing genes GSTT1 and CYP1A1 in sudden infant death syndromeAmerican Journal of Medical Genetics Part A, 2006
- Developmental changes in the expression of growth hormone-releasing hormone and pituitary adenylate cyclase-activating polypeptide in zebrafishJournal of Comparative Neurology, 2002
- Infection, inflammation and sleep: more pieces to the puzzle of sudden infant death syndrome (SIPS)APMIS, 1999
- Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genesEuropean Journal of Pediatrics, 1989